Natural insect repellent

ABSTRACT

A topical insect repellent with extended duration of protection was obtained from mixtures of molecules based on two or more volatile repellent organic molecular species occurring naturally on the human skin surface. The novel repellent comprises mixtures of lower, intermediate, and higher volatility organic molecules. Active ingredients for formulations are obtained from homologous series of carboxylic acids, alcohols, ketones, and lactones which span a similar range of volatility and which occur naturally on the skin surface. Volatile silicone fluid imparts mildness and water repellency to the repellent formulations. The new natural repellent exhibits the longevity and repellency that is comparable to N,N-diethyl-m-toluamide (DEET), a synthetic compound employed in almost all commercial formulations, but the inventive natural repellent is more acceptable than DEET, which has an unpleasant odor and imparts a greasy feel to the skin. The inventive insect repellent, formulated in a volatile silicone fluid, was shown to repel and incapcitate stable flies. This finding demonstrated that repellency was not limited to mosquitoes, but extends to other biting flies or insects, thus demonstrating the utility of the novel insect repellent for protecting pets and livestock as well as humans.

I. BACKGROUND OF THE INVENTION

[0001] This application claims the benefit of prior U.S. applicationSer. No. 60/051,320, filed Jun. 30, 1997 and is incorporated herein byreference.

[0002] 1. Field of the Invention

[0003] This invention relates generally to insect and arthropodrepellents and more specifically to mosquito, fly, tick and miterepellents using biologically based components.

[0004] 2. Description of Related Art

[0005] At the present time, N,N,-diethyl-m-toluamide (DEET) is theactive ingredient of most commercial topical insect repellents (seeTable 1, below), and the current US Army insect repellent (EDTIAR)contains DEET as its active ingredient. The major commercial brands,Off!®, “Deep Woods Off!®, and Cutter®, are all DEET based products andcomprise 85% of insect repellent sales (Consumer Reports Buying Guide,1994 Special Year-End Issue). Consumer Reports tests indicated thatproducts with the highest concentration of DEET lasted the longestagainst mosquitoes, but cautioned that excessive use of DEET could posesome risk, especially for children. Other disadvantages associated withDEET include: It is a synthetic chemical having a limited spectrum ofactivity and a noticeably unpleasant odor; DEET is a powerfulplasticizer and will dissolve or mar many plastics and painted surfaces;DEET plasticizes the inert ingredients typically used in topicalformulations in order to lengthen the time of effectiveness. This leadsto DEET formulations with low user acceptability. TABLE 1 CommercialTopical Insect Repellents Product Manufacturer Ingredients Ben'sBackyard ® Tender DEET, 23% Ben's Max ® Tender DEET, 95% Cutter InsectRepellent ® Miles Inc. DEET, 21.85% Muskol Maximum Strength ® Schering-DEET, 100% Plough Muskol Ultra ® Schering- DEET, 38% Plough Natrapel ®Tender Citronella oil, 10% Off Deep Wood Formula ® S.C. Johnson DEET,28.5% Off Skintastic Insect S.C. Johnson DEET, 7.125% Repellent ® OffSpring Fresh ® S.C. Johnson DEET, 14.25%

[0006] In recent years, a proprietary bath oil (Skin-So-Soft®, AvonProducts, Inc., New York) has been used as a topical insect repellent.Two of its ingredients (diisopropyl adipate and benzophenone) arerepellent to Aedes aegypti (King, W. V. 1954. Chemicals evaluated asinsecticides and repellents at Orlando, Fla. U.S. Dept. of Agriculture,Agriculture Handbook No. 69:1-397). However, the bath oil was reportedas less effective and less persistent than DEET (Rutledge et al., 1982,Repellent activity of a proprietary bath oil (Skin-So-Soft), MosquitoNews:42:557-559).

[0007] Efforts to develop a natural insect repellent have motivatedstudies of oils of citronella, turpentine, pennyroyal, cedarwood,eucalyptus and wintergreen, but these are relatively ineffective(Handbook of Nonprescription Drugs, 1993, 10th Ed., AmericanPharmaceutical Assn., Washington, D.C.). Consumer Reports testsindicated that “natural products” and products without DEET, includingSkin-So-Soft®, provided little or no protection against mosquitoes(Consumer Reports Buying Guide, 1994 Special Year-End Issue). Insectrepellents for nonprescription oral use are not generally recognized assafe and effective (Federal Register, 1985, 50:25170).

[0008] Franz Bencsits describes “Use of First Runnings Coconut FattyAcid as Insect-repellent” in U.S. Pat. No. 5,594,029. Although Bencsitsdoes not describe specifically what “first runnings” of coconut fattyacids are, he describes that combining the “first runnings” with “. . .another active substance, an oil or fat selected from the groupconsisting of rape-seed oil, sunflower oil, peanut oil/butter, . . . ”etc. provides an insect repellent. Because the term “first runnings” isnot a term of art and is not understood by the average knowledgeableperson working in the field, it is impossible to know exactly whatsubstance Bencsits tested. The average knowledgeable person working inthe field of formulating insect repellents does not know what “firstrunnings” are or how to obtain them. Many experts also do not understandthis term and were not able to discover its meaning even with research.Furthermore, the limited number of tests and controls, and lack ofattention to fatty acids as potential skin irritants appear to limitBencsits' invention to non-animal surfaces.

[0009] Bencsits teaches the use of up to 15% potassium hydroxide (KOH)in his formulations. KOH ionizes fatty acids, turning them intonon-volatile salts. Bencsits thus teaches away from the utility ofvolatile compounds.

[0010] Bernard Crammer, et al. Describes in U.S. Pat. No. 5,064,859, amethod for killing lice and lice eggs that have infested human skin andhair with a C₈ to C₁₂ alkyl radical. The patent does not mentionrepelling live approaching insects.

[0011] Stephen Herman describes, in U.S. Pat. No. 5,093,326, acomposition comprising an ozonized derivative of unsaturated hydrocarbonfor repelling insects from a surface. Performance does not appearcompetitive with DEET.

[0012] Clearly there is a need for a long-lasting effective insectrepellent that is pleasant to use and that will not damage plasticcontainers, or the text printed on the containers.

II. SUMMARY OF THE INVENTION

[0013] It is an object of the present invention to provide an insect andarthropod repellent that is safe, long-lasting, effective and pleasant.It is a further object for the inventive formulation to avoid the damageto plastic containers and the text printed on the containers that isassociated with currently effective insect repellent formulations.

[0014] The present inventive insect and arthropod repellent comprises acombination of two or more homologous volatile repellent molecules,similar or identical to those normally found on human skin, wherein atleast one of the molecules has a vapor pressure between about 0.1 mm Hgand about 10 mm Hg at 125° C. and at least one other molecule has avapor pressure between about 5 mm Hg and about 100 mm Hg at 125° C.

III. SUMMARY DESCRIPTION OF THE DRAWINGS

[0015]FIG. 1: illustrates the evaporation rate of such a hypotheticallong-lasting repellent having a relatively constant evaporation ratesufficiently above the MEER to maintain effective repellency.

[0016]FIG. 2: shows schematic diagram of a Skin Penetration/Evaporationlaboratory apparatus.

[0017]FIG. 3: shows the percent repellency of homologs containing 8 to11 carbon atoms applied to gauze, compared to DEET.

[0018]FIG. 4: shows the percent repellency of homologs containing 8 to11 carbon atoms applied to skin, compared to DEET. The repellencydropped dramatically with increasing numbers of carbon atoms.

[0019]FIG. 5: shows a graph of percent repellency two hours after skinapplication. 4-methyloctanoic acid (4MOCTAN) and nonanoic acid (C9) hadthe highest repellency.

[0020]FIG. 6: shows a graph comparing the percent repellency of 0.3 and0.6 mg/cm² 4MOCTAN and 0.3 mg/cm² DEET over a 4 hour period. Taking intoconsideration that about 50% of the 4MOCTAN ionizes at skin pH, therepellency of 4MOCTAN is nearly equal to that of DEET.

[0021]FIG. 7a: shows a graph of percent repellency vs. time for each ofthe three molecules, octanoic acid C8, nonanoic acid C9, and decanoicacid C10 compared to DEET.

[0022]FIG. 7b: shows a graph of percent repellency vs. time for a 1:1:1mixture of octanoic acid (C8), nonanoic acid (C9), and decanoic acid(C10), each at a topical dose of 0.2 mg/cm², and 0.3 mg/cm² DEET. TheC8C9C10 combination gave repellency at 8 hours after applicationcomparable to that of DEET at 4 hours.

[0023]FIG. 8: shows a diagram of a modified Feinsod-Spielmanolfactometer.

[0024]FIG. 9: shows a histogram of olfactometer scores, which measureattractancy of female test subjects. A higher number designates greaterattractancy.

[0025]FIG. 10: shows a histogram of olfactometer scores, which measureattractancy of male test subjects. A higher number designates greaterattractancy.

[0026]FIG. 11: shows a plot of female test subject olfactometer scores,which measure attractancy, vs. age.

[0027]FIG. 12: shows a plot of male test subject olfactometer scores,which measure attractancy, vs. age.

[0028]FIG. 13: shows the change in evaporation rate of DEET over time,and of a mixture of equal concentrations of C₈, C₉, and C₁₀; thestraight line represents the minimum effective evaporation rate forDEET.

[0029]FIG. 14: shows a comparison of the repellency of formulatedC8C9C10 vs Skintastic against Aedes aegypti mosquitoes.

IV. DETAILED DESCRIPTION OF THE INVENTION

[0030] The present invention comprises an inventive formulation forapplication to skin that has a natural pleasant feel, which is made fromfatty acids or other organic molecular species normally found on manypeople's skin, and which is approximately as effective as DEET both interms of repellency and duration of effect. The active repellentmolecules have a polar group attached to a non-polar group comprisingbetween about three and about twelve carbon atoms. The non-polar groupmay comprise a branched carbon chain or an unbranched carbon chain. Thepolar group may comprise carboxyl, alcohol, ketone, lactone or otherpolar groups. An effective formulation or composition or repellentmolecules comprises molecules having at least two differentvolatilities. To achieve such a mixture, homologous molecules havingdifferent lengths unbranched carbon chains can be used because shorterunbranched carbon chains are more volatile than longer unbranched carbonchains. Another method of achieving a mixture of volatilities is to mixhomologous molecules having a branched non-polar chain with moleculeshaving different (or no) branching configurations of the same number ofcarbons. It will be obvious to chemists of ordinary skill that a mixturecomprising various other combinations of homologs and isomers of anactive repellent molecule will result in a combination of volatilities.

[0031] The inventive formulation comprises a combination of two or morehomologous volatile repellent molecules, similar or identical to thosenormally found on human skin, wherein at least one of the molecules hasa vapor pressure between about 0.1 mm Hg and about 10 mm Hg at 125° C.and at least one other molecule has a vapor pressure between about 5 mmHg and about 100 mm Hg at 125° C. Preferably the molecules are freefatty acid carbon chains having between 3 and 12 carbon atoms and apolar group on one end.

[0032] Preferably the repellant molecules are mixed in adermatologically acceptable carrier. The carrier allows the formulationto be adjusted to an effective concentration of repellant molecules. Thecarrier may further provide water repellency, prevent skin irritation,and/or soothe and condition skin. For example the carrier may includesilicone, petrolatum, lanolin or many of several other well know carriercomponents.

[0033] Insect repellents form an unusual class of compounds whereevaporation of the active ingredient from the skin surface is necessaryfor effectiveness. An evaporation rate greater than the minimumeffective evaporation rate (MEER) results in a significant andundesirable mode of loss. Penetration into and through the skin is alsoan undesirable mode of loss of compound from the skin surface. In thepast, researchers attempted to balance these properties by finding asingle active ingredient having the right balance of physicalproperties. Alternatively, the active ingredient was formulated withpolymers and inert ingredients added to the active ingredient for thepurpose of modifying the persistence of the active ingredient on theskin surface. Adding inert ingredients to the active ingredient limitsthe number of molecules of active ingredient on the surface of therepellent film. Since a molecule must be on the surface in order toevaporate, the evaporation rate is lowered. This carries with it thenegative consequence of diluting the concentration of active ingredientthat can be applied to the skin which in turn reduces the overallpotency of a formulation containing inert ingredients. In anotheralternative, the active ingredient was contained in microcapsules tocontrol rates of loss from the skin surface. Another technique oflimiting the evaporation rate of active ingredient was to synthesize aprecursor molecule, which slowly disintegrated on the skin surface torelease the active ingredient.

[0034] Desirable properties of a topical insect repellent include lowtoxicity, resistance to loss by water immersion or sweating, low or noodor or at least a pleasant odor, ease of application, and rapidformation of a dry tack-free surface film. Attempts to improve theproperties of DEET through polymer or microcapsule formulation have beenfrustrated by DEET's plasticizing properties, which lead to a high tackskin surface.

[0035] The present invention makes use of a novel method of developing aan optimal topical repellent, firstly by deriving the active ingredientsfrom chemicals already naturally found on the skin and secondly, byusing homologs of the active ingredient to optimize evaporation rate.Since the homologs also possess repellent activity, as opposed to inertingredients which do not, the amount of active repellent on the skinsurface is maximized.

[0036] When formulating the insect repellent composition it is importantto combine a volume repellent molecules having relatively highvolatilities with a volume of repellent molecules having a lowervolatility which will remain on the skin longer. One way to achieve amixture of volatilities is to mix organic molecules having unbranchedchains of differing chain lengths, that is mixing shorter carbon chainswhich are more volatile with longer carbon chains. Preferably theshorter chains have between about 6 and about 8 carbon atoms permolecule. Preferably the longer chains have between about 9 and about 12carbon atoms per molecule.

[0037] A wide variety of compounds possess insect repellent and/ormosquito repellent activity, as evidenced by the diversity of chemicalstructures reported by the USDA (Chemicals Evaluated as Insecticides andRepellents at Orlando, Fla., compiled by W. V. King, US Department ofAgriculture, Agricultural Research Service, Agriculture Handbook No. 69)to contain repellent activity. Activity is found in alcohols, amides,esters, ketones, acids, lactones, lactams etc., and positional isomersof DEET or the diasterioisomers of ethyl hexanediol, both well studiedrepellents, have similar repellent activity. Activity does appear todepend on the physical properties of these compounds. One property thatis important is surface activity, as most, if not all, repellentscontain both polar and non-polar regions in their structure. A secondproperty is volatility. Because mosquitoes' sensory receptors formosquito repellents such as DEET are located on the mosquito antenna,effectiveness of a repellent compound depends on it's volatility fromthe skin surface. It is desirable for the repellent compound to reachthe mosquito antenna before the mosquito lands on the skin. Whenmosquitoes' antenna are removed, they are not repelled by DEET. Manyyears of observations of mosquito behavior reveal that biting occursshortly after mosquitoes begin to land on repellent treated skin.

[0038] Therefore, the evaporation rate of repellents from the skinsurface is an extremely important factor in the ability of repellents toprotect the skin from bites. A certain minimum concentration ofrepellent is needed in the air space directly above the skin surface inorder to repel insects, and this concentration is a measure of thepotency of the repellent. To maintain this concentration, each repellentmust have a minimum effective evaporation rate (MEER) from the skinsurface. The MEER will change as a function of conditions in the field.For example, as the avidity or biting tendency of a mosquito increases,a higher MEER will be required. Another important factor that influencesthe MEER is the concentration of mosquitoes. For example, in anenvironment having a low concentration of mosquitoes where thosemosquitoes were not hungry, the MEER could be as low as 2, or morecommonly 5, or 6. In an environment having a high concentration ofhungry mosquitoes the MEER might be as high as 12 or even 15. In manyenvironments, a MEER of about 9 or 10 is required, as indicated in FIG.1.

[0039] The evaporation rate of a compound from the surface of the pureliquid will be a function of its vapor pressure (VP) and molecularweight (M), as given by equation (1), where f is a constant (W. F.Spencer and W. J. Farmer, Assessment of the Vapor Behavior of ToxicOrganic Chemicals, in Dynamics, Exposure and Hazard Assessment of ToxicChemicals, R Haque, ed, Ann Arbor (1980), pp. 143-161).

Evaporation rate (bulk liquid)=f(VP)(M)^(0.5)   (1)

[0040] When a repellent is applied in small doses to the skin surface,the evaporation rate is determined by many factors, including the rateof skin absorption. The evaporation rate will decrease with time (t) inproportion to the amount of chemical remaining on the skin surface andcan be approximated by equation (2), where A is the evaporation rate att=0 and e and k are constants.

Evaporation rate (skin surface)=Ae ^(−kt)   (2)

[0041] At a certain time point (t_(d)) after topical application, theevaporation rate of a repellent from skin becomes less than the MEER andbiting will occur. The time t_(d) represents the effective duration ofrepellent protection. A long lasting repellent for the skin would havean a relatively constant evaporation rate (a low value of “k” inequation 2) that is sufficiently above the MEER. FIG. 1 illustrates theevaporation rate of such a hypothetical repellent. The insect repellentDEET was the result of an intensive search by the USDA to find such acompound. Unfortunately though, DEET repellency varies with itsevaporation rate, which can be different in a laboratory instrument suchas the “Skin Penetration/Evaporation Apparatus” shown in FIG. 2 and inreal field conditions. Measured with the apparatus shown in FIG. 2,DEET's evaporation rate immediately after application is much higherthan the MEER; the rate decreases rapidly thereafter. Under laboratoryconditions DEET provides only 5-7 hours of protection and much less thanthat under summer field conditions.

[0042] Many attempts have been made to formulate DEET with inertingredients to reduce its initially excessive rate of evaporative and toextend the time interval when the evaporation rate is above the MEER.However, DEET plasticizes or partially dissolves many of thesematerials, rendering them ineffective or creating a sticky formulationunacceptable for use on the skin. This approach also suffers from thefact that only a certain total amount of repellent formulation can beapplied to the skin surface and that the addition of inert ingredientsto the formulation decreases the amount of active that can be applied.Generally, the ratio (by weight) of added inert ingredient to DEET mustbe at least 3-4 before the additive begins to significantly affectDEET's evaporation rate (Evaporation and Skin PenetrationCharacteristics of Mosquito Repellent Formulations, W. G. Reifenrath, G.S. Hawkins and M. S. Kurtz, J. Am. Mosq. Control Assn., 5:45-51, 1989).

[0043] Naturally occurring fatty acids contain both polar (carboxylicacid group) and non-polar (alkyl chain) regions in their structure andthe lower molecular weight homologs are sufficiently volatile toevaporate from the skin surface. Individually, these compounds haverepellent activity. A number of these compounds were applied tonon-absorptive gauze mounted between the human forearm and theolfactometer containing mosquitoes. These tests were done immediatelyafter application to minimize losses due to evaporation (described fullyin “Example 2” below). Because skin absorption and evaporative loss isminimized, this test can be regarded as a measure of the potency of thecompounds. Homologs containing 8 to 11 carbon atoms had similar potency(percent repellency), which was greater than that of DEET (FIG. 3). Sixcarbon homologs and twelve carbon homologs had potency equal to or lessthan DEET. These results focused attention on carboxylic acidscontaining six to twelve carbon atoms. When the repellency of compoundswithin this range was determined immediately after application to skin(described in Example 2, below), only the saturated derivatives octanoicacid (C8) and 4-methyloctanoic acid (4MOCTAN) had repellency comparableto DEET and the unsaturated derivatives 2-octenoic acid (2OCTEN) and3-methyl-2-octenoic acid (3M2OCTEN) were less repellent (FIG. 4).Percent repellency dropped dramatically with increasing numbers ofcarbon atoms in the molecule (FIG. 4). Two hours after skin 2application, 4-methyloctanoic acid (4MOCTAN) and nonanoic acid (C9) hadthe highest repellency (FIG. 5). The nonanoic acid was preferablysaturated. 4MOCTAN had the best overall performance at the zero and twohour time points. It should be noted for FIGS. 4 and 5 that thecarboxylic acids exist on the skin at a pH which ionizes 50% of themolecules (pH=pKa of the acids). Since the ionized species are notvolatile, the actual available dose is approximately 50% of that forDEET. Taking this factor into consideration, the repellency of 4MOCTANat 0.6 mg/cm² is nearly equal to that of DEET over a 4 hour period (FIG.6). However, 4MOCTAN is thermally unstable and is not generallyavailable commercially.

[0044] Rather than conduct a time-intensive search for a singlecarboxylic acid with optimal repellent properties and user acceptability(many short chain fatty acids have very strong, objectionable odors), amixture of repellent fatty acids spanning a range of volatility wasinvestigated. In theory, molecules in a mixture “compete” with eachother for evaporative loss from the skin surface, and the initialevaporation rate of each component will be lower than that of an equaldose of pure component. Initially, each component would be expected toundergo approximately the same percentage reduction in evaporation rateif the components are present in equal amounts. The component with thehighest vapor pressure will have the greatest reduction in componentmass entering the air space over the skin. At later time points, theevaporation rate of each component will be higher than that of an equaldose of pure component. Again, the component with the highest vaporpressure will have the greatest increase in component mass entering theair space over the skin. Mixing less volatile, but still active, longerchains with the more volatile shorter chains, results in a constantevaporation of active repellent molecules from the surface of the filmof the inventive insect and arthropod repellent after it is applied tothe skin, hair or clothing of the user. The net result of the mixturewill be reduction in the initial excessive evaporation of the mostvolatile repellent component and, at longer time points, a higher totalrate of evaporation of repellent molecules into the air space over theskin. Such a result will lead to a composition with extended duration ofprotection. Specifically, we found that a 1:1:1 mixture of octanoic acid(C8), nonanoic acid (C9), and decanoic acid (C10), each at a topicaldose of 0.2 mg/cm², was found to give repellency at 8 hours afterapplication comparable to that of DEET at 4 hours. FIG. 7A shows thepercent repellency of each component by itself, and FIG. 7B shows thepercent repellency of the inventive repellent combining two or moremolecules having different volatilities. An additional advantage of thismixture is the ability to easily change the ratio of components to suitconditions. If mosquito avidity or biting pressure is very high (theFlorida everglades, for example), the mixture may fail immediatelybecause the initial evaporation rate does not exceed the MEER. In thiscase, the proportion of C8, the most volatile component, could beincreased to provide effective repellency, although some loss ofduration would be expected.

[0045] The relative concentrations of molecules having more and lessvolatility used in a particular formulation can vary greatly dependingon the needs of the user. Where it is easy to reapply repellent, ahigher percent of the shorter, more volatile molecules is used; where itis important to have long lasting protection, a high percent of thelonger, less volatile molecule is used.

[0046] As stated above, the shorter chains preferably have between about6 and about 8 carbon atoms per molecule and the longer chains preferablyhave between about 8 and about 12 carbon atoms per molecule.

[0047] For example, the shorter chain component can vary between 1% and99% of the active ingredients. More preferably it varies between about10% and about 90% of the active ingredients. Alternatively, it variesbetween about 40% and about 60% of the active ingredients. The longerchain component can also vary between 1% and 99% of the activeingredients. More preferably it varies between about 10% and about 90%of the active ingredients. Alternatively, it varies between about 40%and about 60% of the active ingredients.

[0048] For many application it is most desirable to have three or morevolatility ranges present in the active ingredients. One example wouldbe a mixture in which relatively short, intermediate, and long chainswould be present. The percentages with which these components are mixedfor a given application will quickly become apparent to one of ordinaryskill in the art. When mixing more than two unbranched chain sizes inthe repellent, the shorter chain component preferably has between about6 and about 8 carbon atoms per molecule, the intermediate chaincomponent has between about 8 and about 9 carbons per molecule, and therelatively longer chain component has between about 9 and about 12carbons per molecule.

[0049] The high volatility component can vary between 1% and 99% of theactive ingredients. More preferably it varies between about 10% andabout 70% of the active ingredients. Alternatively, it varies betweenabout 20% and about 50% of the active ingredients. The intermediatevolatility component can vary between 1% and 99% of the activeingredients. More preferably it varies between about 10% and about 70%of the active ingredients. Alternatively, it varies between about 20%and about 50% of the active ingredients. The lowest volatility componentcan vary between 1% and 99% of the active ingredients. More preferablyit varies between about 10% and about 70% of the active ingredients.Alternatively, it varies between about 20% and about 50% of the activeingredients.

[0050] Among molecules having unbranched carbon chains, those moleculeshaving shorter chains have higher volatility than longer chains.Additional modifications in volatility of the component compounds aremade by modifying the branching of the chains. Generally branching on achain increases volatility.

[0051] The inventive repellent comprises a novel combination of organicmolecules, having different evaporation rates, where vapor pressure isrelated to the evaporation rate. Thus, one formulation of the inventiverepellent comprises a mixture of three straight chain molecules, such asoctanoic acid, nonanoic acid, and decanoic acid. An alternateformulation comprises a mixture of, for example, straight chain C-10(decanoic acid) combined with branched ten-carbon molecules such as4-methyl nonanoic acid. Any combination organic molecules having theappropriate volatilities to balance immediate and long-termeffectiveness may be used to formulate the inventive repellent. Straightchain and branched chain organic molecules are combined to achieve thisbalance as well as combinations of straight-chain lengths orbranched-chain molecules having the same or different numbers ofcarbons. The choice of which organic molecules to use in the inventiverepellent is governed by factors such as commercial availability, cost,repellency, evaporation rate, odor, and stability.

[0052] Review of literature in the general field of the invention:

[0053] There is ample evidence that human skin emanates both attractantand repellent compounds for mosquitoes. No single compound is likelyresponsible for mosquito attraction; the same can be said for mosquitorepulsion. The interaction of these compounds is probably of importancein the overall response of the mosquito. Brown (Brown A. W. A., H. P.Roessler, E. Y. Lipsitz and A. G. Carmichael. Factors in theattractiveness of bodies for mosquitoes. The Canadian Entomologist96:102-103, 1964.) lists a number of factors involved in the attractionof mosquito to man (in order of importance): moisture, convective heat,carbon dioxide, movement, contour or increase in black-white interfaces,and reflectivity. The influence of carbon dioxide as a mosquito“activator” has long been recognized (Rudolphs, W. Chemotropism ofmosquitoes. New Jersey Agricultural Experiment Station Bulletin No. 367,1922). However, Acree and coworkers (Acree, F, R. B. Turner, H. K.Gouck, M. Beroza and N. Smith. L-Lactic Acid: A mosquito attractantisolated from humans. Science, 161:3846-7, 1968) have shown that carbondioxide does not attract mosquitoes in purified air alone. Thiel andLaarman found that air swept over the arm was attractive even thoughcarbon dioxide and moisture had been removed; they concluded thepresence of other attractants or odors was responsible for theattraction (Van Thiel, P. H. and J. J. Laarman. What are the reactionsby which the female Anopheles find its blood supplies? Acta Leidensia24:180-187, 1954). Snow (Snow, W. F. The effect of a reduction inexpired carbon dioxide on the attractiveness of human subjects tomosquitoes, Bull. Ent. Res. 69:43-48, 1970) studied mosquito attractionto normal subjects and to subjects wearing a breathing apparatus toremove most of the exhaled carbon dioxide. Fewer mosquitoes wereattracted to the subjects with reduced carbon dioxide output. However,when the mosquitoes were in close range of the host, the experimentaltreatment had no effect on the proportion of mosquitoes attempting tofeed. Snow concludes from this study that carbon dioxide, originatingfrom the lung, may be more important as a long range attractant. Reportsby Rahm (Rahm, U. Zum problem der attraktion von stechmucken durch denmenschen, Acta Trop., 13:319-344, 1956) and Brouwer (Brouwer, R. Theattraction of carbon dioxide excreted by the skin of the arm of malariamosquitoes, Trop Geogr. Med. 12:62-66, 1960) showed that carbon dioxideoutput from the skin was insignificant in stimulating mosquitoes. Incontrast to these findings, Khan et al. (Khan, A. A., H. I. Maibach, W.G. Strauss, and W. R. Fenley. Quantitation of effect of several stimulion the approach of Aedes aegypti, J. Econ. Entomology 59:690-694, 1966)concluded that heat and carbon dioxide are important for the approach ofmosquitoes to the host at close proximity, and that odor was moreimportant at greater distance. Carlson et al. (Carlson, D. A., C. E.Schreck, and R. J. Brenner, Carbon dioxide released from human skin:effect of temperature and insect repellents; Journal of MedicalEntomology 29:165-170, 1992) measured the amount of carbon dioxide givenoff by the hand at 1.0-1.8 ml/h under laboratory conditions. The authorsconcluded that this amount of carbon dioxide is negligible compared toambient levels and was unlikely to be attractive to mosquitoes byitself.

[0054] In 1958, Brouwer (Brouwer, R., Acad. Proefschr. Leiden, 110p,1958) reported consistent differences in attraction of Anophelesstephensi to humans that were independent of moisture, warmth and carbondioxide. He concluded that the differences were due to sweat or bodyodor. Schreck (Schreck, C. E. and J. James, Broth culture of bacteriathat attract female mosquitoes, Mosquito News 28:33-38, 1968) reportedthat a polyethylene glove, worn for 1 hour, remained attractant tomosquitoes over a 3 hour period after removal from the hand. Thompsonand Brown demonstrated the attractiveness of sweat was decreased by therelease of volatile acids (Thompson, R. P. and A. W. A. Brown; Theattractiveness of human sweat to mosquitoes and the role of carbondioxide; Mosquito News 15:80-84, 1955).

[0055] Gilbert et al. studied 50 men and 50 women to determine theirattractiveness to Aedes aegypti mosquitoes (Gilbert, I. H. G. K. Gouckand N. Smith; Attractiveness of men and women to Aedes aegypti andrelative protection time obtained with DEET; The Florida Entomologist49:53-66, 1966). The 50 women subjects were, on average, less attractivethan the 50 men. However, there was considerable overlap in the rangesof attraction, and many of the women were more attractive than some ofthe men. However, only two of the most attractive 10 subjects werewomen, and all of the least attractive 10 were women. A possiblerelationship between attraction and differences in skin lipidcomposition was not investigated. Roessler hypothesized that changes inthe attractiveness of females with the menstrual cycle were caused bychanges in estrogen evaporation from the skin (Roessler, P.; Theattractiveness of steroids and amino acids to female Aedes aegypti;Proceedings of the Fiftieth Annual Meeting, New Jersey MosquitoExtermination Association and Nineteenth Annual Meeting, AmericanMosquito Control Association, Atlantic City, March 1963, pp. 250-255).

[0056] In a 1968 report, Acree et al. found a correlation between theattractiveness of individuals to mosquitoes and the quantity of lacticacid present in acetone washings of hands. Attractive material was firstobtained by condensation of a nitrogen stream above the skin. However,the amount of material obtained was too small for analytical methodsavailable at that time. These workers noted that the attractancy oflactic acid was not evident without the presence of carbon dioxide.

[0057] Price et al studied the attraction of mosquitoes to humanemanations in a dual port olfactometer (Price, G. D., N. Smith and D. A.Carlson; The attraction of female mosquitoes (Anopheles quadrimaculatusSAY) to stored human emanation in conjunction with adjusted levels ofrelative humidity, temperature, and carbon dioxide; J. Chemical Ecology5:383-395, 1979). Mosquitoes (female Anopheles quadrimaculatus SAY) werepreferentially attracted to the “emanation” air, even though excesscarbon dioxide or water had been added to control air withoutemanations.

[0058] In 1961, Brown and Carmichael reported that lysine free base wasa mosquito attractant (Brown, A. W. A. and A. G. Carmichael; Lysine as amosquito attractant; Nature 169:508-509, 1961). Lysine was known to bepresent in human sweat (Hier, S. W. T. Cornbleet and 0. Bergeim; J.Biol. Chem. 166:327, 1946). Although other amino acids had mosquitoattractant properties, they were considerably less attractant thanlysine. The attractiveness of lysine was later found to be proportionalto the presence of carbon dioxide (Lipsitz, E. Y. and A. W. A. Brown;Studies on the responses of the female Aedes mosquito: IX The mode ofattractiveness of lysine and other amino acids; Bull. Entomo. Res. 54675-687, 1964).

[0059] Strauss et al., surveyed hospitalized patients with variousdiseases and taking various medications for their attractiveness tomosquitoes by a mosquito probing technique. No drug, vitamin, or diseasewas associated with unattractiveness, with the possible exception ofuntreated myxedema (Strauss, W. G. H. I. Maibach and A. A. Kahn; Drugsand disease as mosquito repellents in man; Am. J. Trop Med. Hyg.17:461-464, 1968).

[0060] In addition to the compounds mentioned above, USDA investigatorshave studied 1-octen-3-ol as a mosquito attractant (Kline, D. L. D. A.Dame and M. V. Meisch; Evaluation of 1-octen-3-ol and carbon dioxide asattractants for mosquitoes associated with irrigated rice fields inArkansas; J. Am. Mosq. Control Assoc. 7:165-9, 1991). Israeliinvestigators found that although sheep were attractive to Culex pipiensL. and Aedes caspius (Pallas), few Culex pipiens and no Aedes caspiusengorged. The investigators suggested that sheep may possess, inaddition to the mechanical protection afforded by wool, a close-actingrepellent that deters the mosquitoes from biting. The repellent was notidentified.

[0061] Maibach and coworkers report the observation that the attractancyof human sweat increased significantly when lipids were removed(Maibach, H. I. A. A. Khan, W. G. Strauss and W. A. Skinner; Human skinin relationship to mosquito attraction and repulsion; ConnecticutMedicine, 33:23-28, 1969). Schreck and coworkers isolated a materialfrom glass beads previously handled by humans (Schreck, C. E., N. Smith,D. A. Carlson, G. D. Price, D. Haile and D. R. Godwin; A materialisolated from human hands that attracts female mosquitoes; Journal ofChemical Ecology, 8:429-438, 1981). This residue was found to beattractant to female Aedes aegypti and Anopheles quadrimaculatus Saymosquitoes. This residue was characterized as volatile, and stable onrefrigerated storage for up to 60 days. The residue was not purified orchemically analyzed. Skinner et al. obtained human skin-surface lipidsfrom ether washings of elbows from a number of volunteers (Skinner, W.A. H. C. Tong, H. I. Maibach and D. Skidmore; Human skin-surface lipidfatty acids—mosquito repellents; Experientia 26:728-730, 1970). Thismixture was found to be repellent to Aedes aegypti mosquitoes. Vacuumdistillation, gas chromatography and thin layer chromatography were usedto isolate components from the mixture. The organic fraction of thelipids contained only weakly repellent unsaturated hydrocarbons, withthe major repellent activity present in the more polar fractions.Straight chain carboxylic acids from C-5 to C-13 were found to haverepellent activity in olfactometer tests; higher homologs from C-14 toC-18 had little repellent activity. Straight chain unsaturatedcarboxylic acids from C-9 to C-24 were also found to have repellentactivity. Skinner concluded that unsaturated fatty acids accounted forthe repellency of the free fatty acid fraction of skin surface lipids,based on two findings: 1) no saturated fatty acids below C₁₃ weredetected and higher homologs had little repellent activity inolfactometer tests, 2) unsaturated fatty acids starting with C₁₄ weredetected and these had repellent activity in olfactometer tests. Skinnerthen suggested that mosquito attraction to animals could be reduced byincreasing the amount of unsaturated fatty acids present on the skinsurface. To this end, 2-decenoic acid was tested for mosquito repellentactivity in volunteers at Letterman Army Institute of Research in 1970(Kurtz, A. P.; More Effective Topical Repellents Against Malaria-BearingMosquitoes: Review of Volunteer Tests of Mosquito repellent FormulationsOctober 1969-September 1971, Report No. 13 (Interim Report), LettermanArmy Institute of Research, Presidio of San Francisco, Calif. 94129, May1, 1973). The compound was applied to the forearm at a dose of 0.5mg/cm² and compared to DEET at the same dose. Application sites werechallenged with Aedes aegypti mosquitoes. Although 2-decenoic acidshowed repellent activity, its average duration of protection wasshorter than that of DEET and its range of protection time was largerthan that of DEET (Table 2). Skinner also reported the evaluation of anumber of unsaturated fatty acids on the skin of man (Table 3). However,none provided longer protection time than DEET. It should be noted thatthis line of investigation was based on fatty acids recovered from skinsurface wipes and not on the skin's chemical vapor, which is responsiblefor host seeking behavior. The significance of the volatile compoundswas therefore underestimated. TABLE 2 Test of Decenoic acid forrepellency against Aedes aegypti on the skin of man (reference Kurtz,LAIR Report No. 13, 1973)^(a) Protection Time Protection Time Compound(hours) Range (N) Decenoic acid 0.5 6 ± 4 0.5-12.5 (14) mg/cm² DEET, 0.5mg/cm² 8 ± 2 3.5-12.0 (10)

[0062] TABLE 3 Protection time of unsaturated carboxylic acids (0.31mg/cm², reference Skinner, W.A., Attractiveness and Repellency of Man toMosquito Bites, DTIC Report No. AD693891, October, 1969) Protection timeagainst Compound Aedes aegypti mosquitoes 2-Nonenoic Acid (unsat C-9) 2h 2-Decenoic Acid (unsat C-10) <15 min. Undecylenic Acid (unsat C-11)3.5 h 2-Dodecenoic Acid (unsat C- 2 h 12) Oleic Acid (unsat C-18) <15min. Linoleic Acid (unsat C-18) <15 min. Linolenic Acid (unsat C-18) <15min. Arachidonic Acid (unsat C-20) <15 min. DEET (reference) 5.5 h

[0063] A number of a straight chain carboxylic acids were reported in1954 to have repellent activity (King, W. V., Chemicals evaluated asinsecticides and repellents at Orlando, Fla. Agriculture Handbook No.69; Entomology Research Branch, Agricultural Research Service, U.S.Department of Agriculture, Washington, D.C., 1954. p. 185). None,however, provided protection time equal to that of DEET (Table 4).Quintana and coworkers realized the short-comings of these compounds andattempted to improve their protection time by the preparation ofcarboxylic acid esters designed to adhere to the stratum corneum andslowly release the active component (free acid) on hydrolysis of theester (Quintana, R. P., Lasslo, A., Garson, L. R., Chemical Studies inConnection with Potential Systemic Insect-Repellents and ProphylacticAgents Deposited in the Skin; Report No. 4, Research Contract No.DA-49-193-MD-2636, U.S. Army Medical Research and Development Command,Office of the Surgeon General, Washington, D.C. 20315). However, thesecompounds did not result in a repellent with improved duration ofprotection over DEET. TABLE 4 Protection time of saturated carboxylicacids applied to human skin at a dose of approximately 2 mg/cm².^(a)Protection Protection time time against against yellow malaria Compoundfever mosquitoes mosquitoes Caproic Acid (C-6) — — Ethanthic (C-7)121-180 min 90+ min. Caprilic Acid (C-8) — — Pelargonic Acid (C-9) 180+min. 31-60 min. Capric Acid (C-10) 300+ min. 61-90 min. Hendecanoic Acid(C- 300+ min. 90+ min. 11) Lauric Acid (C-12) — — DEET (reference) 363min^(b) — # forearm was exposed in a cage containing a high number(2,000-4,000) of unfed mosquitoes for 3 minutes at intervals ofapproximately 30 minutes until two bites were received (two bites in onetest period or one bite in each of two consecutive test periods). Thetime interval between application and when two bites were received wasdefined as the “protection time”. Against the yellow fever mosquito(Aedes aegypti (L.)), ethanthic acid (C-7) was rated 3 (121-180 min)pelargonic acid # (C-9) was rated 4 (180+ min), capric acid (C-10) wasrated 4A (300+ min.) and hendecanoic acid (C-11) was rated 4A (300+min.). Against the malaria mosquito (Anopheles quadrimaculatus Say),ethanthic acid was rated 4 (90+ min.), pelargonic acid was rated 2(31-60 min), capric acid was rated 3 (61-90 min.) and hendecanoic acidwas rated 4 (90+ min.).

[0064] In a later report, Skinner et al. analyzed acetone extractedlipids from skin using gas chromatography-mass spectroscopy (Skinner, W.A., H. C. Tong, H. Johnson, R. M. Parkhurst, D. Thomas, T. Spencer, W.Akers, D. Skidmore and H. Maibach; Influence of human skin surfacelipids on protection time of topical mosquito repellent; J. Pharm. Sci.,66:1764-1766, 1977). Multiple regression analysis was used to relateattractancy and repellent protection time to the amounts of saturatedand unsaturated fatty acids. Dry protection time or duration ofprotection of the insect repellent N,N-diethyl-3-benzamide (DEET)correlated positively with saturated fatty acids C-11, C-13, C-15 andC-18 and unsaturated fatty acids C-14, C-15, C-16 and C-17; dryprotection time correlated negatively with saturated C-7, C-12 and C-16fatty acids. The fatty acids may affect the protection time of DEET by aphysical mechanism; that is, they may alter the evaporation andpenetration of DEET through their film forming activity. Indeed,repellent protection time of DEET correlated positively with the totalweight of lipid found on the skin. Attractancy, as measured by theaverage number of Aedes aegypti mosquitoes probing the test site of thevolunteer in one minute, was found to correlate positively with C-15unsaturated fatty acid and C-14 saturated fatty acid; attractancy wasfound to correlate negatively with the more volatile C-11 saturatedfatty acid. The authors indicated that the precise identification offatty acid components affecting attractiveness would require furtherstudy.

[0065] There is ample evidence that human skin emanates both attractantand repellent compounds for mosquitoes. However, skin emanations havebeen poorly characterized, and important volatile components were lostin the analysis procedures (Bowen, M. F., The sensory physiology ofhost-seeking behavior in mosquitoes. Annu. Rev. Entomol., 36:139-158,1991). No single compound is likely responsible for mosquito attraction;the same can be said for mosquito repulsion. Although certain fattyacids were found to repel mosquitoes, a practical insect repellent hasnever been developed from these compounds because it was not appreciatedthat optimal evaporation rates from the skin were not achieved. We havedeveloped a long lasting repellent based on a combination of fattyacids, each with the appropriate volatility.

EXAMPLES OF THE INVENTIVE INSECT AND ARTHROPOD REPELLENT EXAMPLE 1:Identification of natural insect repellent compounds on human skin

[0066] Olfactometer: A Fiensod and Spielman olfactometer, as modified byBowen and Davis, measured the host-oriented flight response of femalemosquitoes to volatile host emanations (Feinsod, F. M., and A. Spielman;An olfactometer for measuring host-seeking behavior of female Aedesaegypti (Diptera:Culicidae); J. Med. Entomol., 15:282-285, 1979). Theolfactometer (approximately 38 cm high) consisted of an upper and lowerscreened chamber with a closure between the chambers (FIG. 8). A fanplaced above the upper chamber drew air through the apparatus atapproximately 0.2 m/s. A temperature and humidity controlled chamber (5′wide by 6′ long by 8′- high) was constructed to house the test subjectand the olfactometer.

[0067] Rearing of Mosquitoes: A second environmental chamber, maintainedat 27° C. and 80% humidity, was dedicated to the rearing of Aedesaegypti mosquitoes. Routine shipments of eggs (American BiologicalSupply, Gainesville, Fla.) were used to maintain a continuous supply ofadult 5-10 day old mosquitoes.

[0068] Assays for Attraction of Mosquitoes to Human Subjects: A group of30 volunteers, consisting of 14 females and 16 males and ranging in agefrom 24 to 68 years, was selected from the surrounding civilianpopulation. Individuals were tested for their ability to attract Aedesaegypti mosquitoes contained in the olfactometer. Tests were conductedat a temperature of 27° C. and 50% relative humidity. For each trial 15avid adult female Aedes aegypti mosquitoes (5-10 days post-emergence)were placed in the upper chamber. A small fan was placed on top of theupper chamber to cause an air flow from the lower chamber to the upperchamber. A trial began when the closure between the upper and lowerchamber was opened in the absence of a human host. The number ofmosquitoes entering the lower chamber within a 3 minute period wasrecorded. The volunteer then placed his or her arm beneath the lowerchamber and the number of mosquitoes flying from the upper chamber tothe lower chamber was recorded for the time intervals 0-1, 1-3, 3-5 and5-7 minutes. This trial was repeated twice during a test session toobtain three replicates. Two additional test sessions, at time intervalsof at least 1 week, were conducted to obtain at least 8-9 replicates foreach of 24 subjects. Of the remaining 6 subjects, 3 were tested on twoseparate occasions for a total of 6 replicates per subject; 3 weretested on one occasion for a total of 3 replicates per subject. A totalof 254 tests were conducted.

[0069] Olfactometer scores were calculated for each trial by dividingthe number of mosquitoes entering the lower chamber of the olfactometerduring the 0-1, 1-3, 3-5 and 5-7 minute intervals by the number ofmosquitoes remaining in the upper chamber of the olfactometer at the endof the 3 minute control period. The fractions so obtained was plottedversus time. An equation was fitted to the data and the area under thecurve (olfactometer score) was calculated. An area of 0 (0 mosquitoesentering the lower chamber ×7 minutes) would indicate the subject wascompletely unattractive to mosquitoes. A area of 7 would indicatemaximum attraction.

[0070] Human subjects were identified from a group of 30 males andfemales whose forearms were consistently least attractive to Aedesaegypti mosquitoes contained in an olfactometer (Table 5). Subjects werealso identified who were consistently most attractive to mosquitoes(Table 5). All of the 4 least attractive subjects were female and 10 ofthe 12 least attractive subjects were female. All of the 5 mostattractive subjects were male and 10 of the 12 most attractive subjectswere male. Females in general were significantly less attractive to themosquitoes than the males (ANOVA, F=49.33, P=0.0000). The histograms ofolfactometer response for all trials with female subjects is given inFIG. 9. The corresponding data for male is given in FIG. 10.Olfactometer response did not significantly correlate (P>0.05) with ageof male or female subjects (FIGS. 11 and 12). TABLE 5 Olfactometerresponse of 30 human subjects to mosquitoes. No. of Subject No.Olfactometer Response^(a) Replicates 30 (Female)^(b) 1.73 ± 0.67  3^(c)24 (Female)^(b) 2.13 ± 1.13 9 15 (Female)^(b) 2.65 ± 0.53 8 29(Female)^(b) 2.79 ± 1.44 9 18 (Female) 3.01 ± 1.19 9 26 (Male) 3.06 ±0.97 9 16 (Female) 3.26 ± 1.10 9 1 (Female) 3.34 ± 1.35 18  3 (Male)3.47 ± 1.52 10  27 (Female) 3.56 ± 1.39 9 11 (Female) 3.60 ± 1.19 9 28(Female) 3.65 ± 0.53 6 25 (Male) 3.67 ± 1.49 6 23 (Male) 3.82 ± 1.05 912 (Female) 4.08 ± 1.18 9 10 (Female) 4.22 ± 1.63 3 22 (Male) 4.25 ±0.92 9 17 (Male) 4.33 ± 0.94 9 6 (Female) 4.39 ± 1.51 9 13 (Male) 4.44 ±1.36 9 5 (Male) 4.45 ± 0.62 9 20 (Male) 4.74 ± 0.68 9 4 (Female) 4.92 ±0.88 9 19 (Male) 4.93 ± 0.99 3 21 (Male) 5.03 ± 0.84 6 14 (Male)^(b)5.06 ± 1.11 9 7 (Male)^(b) 5.20 ± 1.11 9 9 (Male)^(b) 5.21 ± 0.85 9 2(Male)^(b) 5.31 ± 0.73 11  8 (Male)^(b) 5.32 ± 0.76 9

EXAMPLE 2: Assay of Compounds for Mosquito Repellency on Gauze orPolyester Film

[0071] Test compounds were dissolved in acetone or ethanol at aconcentration of 150 mg/5 cc. Ethanol solutions of carboxylic acids wereprepared just prior to use. Five hundred microliters of these solutionswere applied to a 50 cm² circular area of a single layer of cotton gauze(Curity Curad gauze, Futuro Inc., Milford, Ohio) or nonwoven polyesterfilm (Reemay 2250, Reemay/Tycon, Inc.). The resultant dose was 0.3mg/cm². Treated gauze or film was allowed to dry in a hood for 3 minutesprior to placement in a cylindrical stainless steel cup (9 cm indiameter and 3 cm in height), whose bottom consisted of stainless steelscreen. The cup was attached to the bottom of the olfactometer (FIG. 8)so that air flowed through the stainless steel screen of the cup,through the treated gauze or film, and through the olfactometer. Avolunteer's forearm was placed under the cup, so that air drawn into thecup and olfactometer was laden with human skin emanations. Tests wereconducted as described in the preceding paragraph, “Assays forattraction of mosquitoes to human subjects”. Percent repellency wasdetermined from the fraction of mosquitoes entering the lower chamberover a seven minute period.

[0072] This assay is an approximate measure of the intrinsic repellencyof a compound. Good repellency in this test is a necessary, but notsufficient, condition for good repellency on skin. Mosquito repellentsmust produce a vapor over the skin surface to confuse the host seekingbehavior of the insect. However, volatilization must not be so greatthat the repellent action rapidly dissipates. Since volatilization fromthe skin will be different from an inanimate surface, skin tests arenecessary to confirm that a compound will be a practical repellent.

[0073] Percent repellency results for various compounds are contained inTable 6. Three of the compounds tested (3M2OCTEN, 3M2PENTEN, andvalerolactam) were found only on the skin of females (Zeng, X. Leyden,J. J. Spielman, A. I. and Preti, G., 1996, Analysis of characteristichuman female axillary odors: qualitative comparison to males; J. Chem.Ecol. 22:237-257). 3M2OCTEN exhibited the greatest repellency (95%),3M2PENTEN repellency (65%) was similar to that of DEET (74%), andvalerolactam had essentially no repellent activity (20%). TABLE 6Percent repellency for various compounds (applied to cotton gauze orpolyester film at a dose of 0.3 mg/cm²) against Aedes aegyptimosquitoes^(a). Carbon Percent Test Compound Atoms Repellency N Ethanol2 7 ± 9 5 Acetone 3 12 ± 10 12  Pentanoic acid^(b) (C-5) 5 not tested(valeric acid) 2-Pentenoic Acid 5 100 ± 0  2 (2PENTEN) Valerolactam 5 20± 22 3 3-Methylpentanoic Acid 6 43 ± 14 2 (3MPENTAN)3-Methyl-2-pentenoic 6 65 ± 16 3 Acid (3M2PENTEN) Octanoic Acid (C-8) 887 ± 1  2 2-Octenoic Acid (2- 8 97 ± 5  2 OCTEN) 4-Methyloctanoic acid 988 ± 18 2 (4MOCTAN) 3-Methyl-2-octenoic acid 9 95 ± 6 6 (3M2OCTEN)Nonanoic acid (C-9) 9 97 ± 5  2 Decanoic acid (C-10) 10  100 ± 0  2Undecanoic acid (C-11) 11  93 ± 0  2 Lauric acid (C-12) 12  69 ± 23 3N,N-Diethyl-m-toluamide 12  74 ± 12 3 (DEET)

[0074] All of the octanoic acid derivatives had good repellent activity,in the range of 87-97% repellency. The pentanoic acid derivatives weregenerally less repellent (43-65%); however, 2-pentenoic acid had 100%repellency. Nonanoic acid (C₉ straight chain), decanoic acid (C₁₀straight chain), and undecanoic acid (C₁₁ straight chain) had goodrepellency (93-100%). Lauric acid (C₁₂ straight chain) had lowerrepellency (69%), similar to DEET. Mosquito repellent activity has notbeen previously reported for the octanoic acid derivatives 3M2OCTEN,2OCTEN, 4MOCTAN, and the pentanoic acid derivatives 3M2PENTEN, 2PENTEN,and 3MPENTAN. Repellent activity has been reported for the straightchain saturated carboxylic acids and certain unsaturated carboxylicacids (See Tables 2, 3 and 4). Some of the saturated carboxylic acidshave also been investigated as mosquito attractants (Knols, B. G. J.,1996, Odour-mediated host-seeking behavior of the afro-tropical malariavector Anopheles Gambiae Giles; Thesis. ISBN: 90-5485-487-1; WageningenAgricultural University; The Netherlands; pp. 213). The results,however, were inconclusive.

[0075] In addition to carboxylic acids, alkanes, alkenes, alcohols,aldehydes, ketones, acids and lactones are known to exist on the skinsurface (Zeng, X., Leyden, J. J., Lawley, H. J., Kiyohito, S., Isao, N.,and Preti, G. 1991, Analysis of characteristic odors from human maleaxillae, Journal of Chemical Ecology, 17:1469-1492) or to volatilizefrom the skin surface (Goetz, N., Kaba, G. Good, D. Hussler, G. andBore, P., 1988, Detection and identification of volatile compoundsevolved from human hair and scalp using headspace gas chromatography,Journal of the Society of Cosmetic Chemists, 39:1-13). Repellentactivity is known to exists in alcohols, aldehydes, ketones, acids(King, W. V., Chemicals evaluated as insecticides and repellents atOrlando, Fla., U.S. Department of Agriculture, Agricultural ResearchService, Agriculture Handbook No. 69) and lactones (Weeks, M. H. andDeSena, B. J. Topical Hazard Evaluation Program of Candidate InsectRepellent AI3-36030 delta-Dodecalactone, U.S. Army Environmental HygieneAgency, Aberdeen Proving Ground, Md., Defense Technical InformationReport No. ADA 040974, March 1976-April 1977).

EXAMPLE 3: Assay of Compounds for Mosquito Repellency on Skin

[0076] Test compounds were dissolved in acetone or ethanol at aconcentration of 300 mg/5 cc. Ethanol solutions of carboxylic acids wereprepared just prior to use. Three hundred and fifty microliters of thesesolutions were applied to a 70 cm² rectangular area of the forearm. Theresultant dose was 0.3 mg/cm². The repellent treated area was allowed todry for 5 minutes prior to test. The treated skin area was placed underthe olfactometer and tests were conducted as described in the precedingparagraph, “Assays for attraction of mosquitoes to human subjects”.Percent repellency was determined from the fraction of mosquitoesentering the lower chamber over a seven minute period.

[0077] A number of compounds were preliminarily investigated for theirability to act as mosquito repellents after topical application (Table7). Some of the more volatile acids (octanoic acid and 4MOCTAN) had meanrepellency (87-93%) that was competitive with that of DEET (95%) shortlyafter application (0 hr). At 2 hours after application, DEET repellencyremained high (89%), while the highest repellency for carboxylic acids(66-73% mean repellency) was found in three of the acids containing 9carbons (3M2OCTEN, 4MOCTAN, and nonanoic acid). The pentanoic acidderivatives were not tested because two of the derivatives had lowrepellency on the gauze/polyester film tests (Table 6) and because thesederivatives are considerably more volatile that DEET (Table 7). Thecompound 2-ethyl-1,3-hexanediol, once a commercial insect repellent, istwice as volatile as DEET and protects against mosquitoes for 3-4 hoursas compared to 5-6 hours for DEET (Hill, J. A., Robinson, P. B., McVey,D. L., Akers, W. A., and Reifenrath, W. G. 1979; Evaluation of mosquitorepellents on the hairless dog; Mosquito News (Journal of the AmericanMosquito Control Association), 39:307-310). Therefore, the pentanoicacid derivatives, having volatilities 17-30 times that of DEET, were notexpected to provide long lasting repellency; these compounds are toovolatile and serve as an upper bound of vapor pressure for a practicalrepellent for carboxylic acids. Decanoic, undecanoic, and dodecanoicacids were less volatile than DEET and had lower 0-h repellency thanDEET (Table 7). Dodecanoic acid demonstrated no repellent effect on skin(Table 7), despite having 93% repellency after application togauze/polyester film (Table 6). This compound was probably notsufficiently volatile from skin and provided a lower bound of vaporpressure for a practical repellent for carboxylic acids. TABLE 7 Percentrepellency for various compounds at various times after applicationagainst Aedes aegypti mosquitoes^(a) Carbon Percent Repellency (N)Compound Atoms Vol.^(b) 0 h 2 h 4 h 8 h No 0 — 9 ± 7 (4) 13 ± 12 (3) 4±6 (2) 17 Treatment (1) 2-Pentenoic 5 92 — — — — acid (est) (3M2PENTEN)3-Methyl-2- 6 49.5 — — — — pentenoic (est) acid (3M2PENTEN) 3-Methypen-6 49.5 — — — — tanoic acid (est) (3MPENTAN) Hexanoic 6 39.6 — — — — acidOctanoic 8 10.8 93 (1) 36 (1) — — acid C-8 2-Octenoic 8 10.8 50 (1) 29(1) 27 (1) — acid (2- (est) OCTEN) 2-Ethyl- 8 6 — — — — 1,3- hexanediol(6-12) 3-Methyl-2- 9 6 (est) 70 ± 24 (2) 40 ± 5 (3) 47 ± 21 60 octerioic(3) (1) acid, 0.3 mg/cm² (3M2OCTEN) 3-Methyl-2- 9 6 (est) 66% (1) 73%(1) 40 (1) — octenoic acid, 0.6 mg/cm² (3M2OCTEN) 4-Methyloc- 9 6 (est)87 (1) 66 (1) — — tanoic acid (4MOCTAN), 0.3 mg/cm² 4-Methyloc- 9 6(est) 93 ± 0 (2) 79 ± 21 (2) 67 ± 9 — tanoic acid (2) (4MOCTAN), 0.6mg/cm² Nonanoic 9 4.8 76 ± 14 (2) 66 (1) 47 (1) — acid (C-9) N,N- 12  395 ± 6 (3) 89 ± 10 (3) 83 ± 9 — Diethyl-m- (3) toluamide (DEET) Decanoic10  2.4 73 (1) 53 (1) 73 (1) — acid (C-10) 2-Decenoic 10  2.4 (est) — —— — acid (2DECEN) Ondecanoic 11  1.5 (est) 40 (1) — — — acid (C-11)Dodecanoic 12  0.57 0 (1) — — — acid (C-12) (est)

EXAMPLE 4: Design of Long Lasting Repellent Formulation

[0078] Octanoic acid, the eight carbon fatty acid, had the highestvolatility of any of the carboxylic acids tested on skin (Table 7) andprovided the best initial repellency (0-h). However, octanoic acid'srepellency rapidly decayed to only 36% at 2-h and reflected theexponential or first order evaporative loss of the compound from theskin surface. The exponential change in the evaporation rate of DEETfrom the surface of excised pig skin is given in FIG. 13. The change inthe evaporation rate of, for example, octanoic acid from the skinsurface would be even greater because it is more volatile than DEET. Arepellent is only effective while the evaporation rate is greater thanits MEER (minimum effective evaporation rate). For DEET that is betweenabout 10 and 15 μgm/cm²⁻hr, as shown by the straight line in FIG. 13. Animpractically large increase in the initial dose, or application level,would be required to extend protection time of molecule with a highevaporation rate. FIG. 13 also shows the change in the evaporation rateof the novel inventive repellent, formulated with equal parts octanoic,nonanoic, and decanoic acids. In contrast to DEET, the inventiverepellent's change in evaporation rate levels off above the MEER.

[0079] Decanoic acid, the ten carbon fatty acid, had the lowestvolatility of any carboxylic acid which provided at least 50% protectionat 0-h. In contrast to octanoic acid, its protection remained relativelyconstant (Table 7), and reflected its constant or zero order evaporativeloss from the skin surface (FIG. 13). Because of the compound's lowvolatility, it is not possible to significantly increase its evaporationrate from the skin surface merely by increasing the dose. Such acompound may provide a long duration of protection if its evaporationrate is just above the MEER or may fail immediately if its evaporationrate is just below the MEER. Test results for decenoic acid, a compoundof similar volatility, are illustrative (Table 2). On two of the testsubjects, the repellent failed immediately, while giving up to 12 hoursof protection for other subjects.

[0080] The results for the nine carbon nonanoic acid (Table 7) areintermediate between the extremes of octanoic acid and decanoic acid. Itis less repellent than octanoic acid at 0-h, but its repellency does notdecay as rapidly. Increasing the dose of related nine carbon acids(3MOCTEN and 4MOCTAN) did not result in a significant increase inrepellency that was competitive with DEET's at 4 hours (Table 7).

[0081] It was known that a mixture of two repellents will decrease theirinitial rate of evaporation and provide a higher level of evaporation atlonger time points (Reifenrath et al., 1989, Evaporation and skinpenetration characteristics of mosquito repellent formulations, Journalof the American Mosquito Control Association, 5:45-51). Based on thispremise, repellents were made having a mixture of the eight, nine andten carbon acids would provide long lasting protection. Test results(Table 8) for this mixture gave protection at 8 hours equivalent to thatof DEET at 4 hours. TABLE 8 Comparison of repellency (% repellencyagainst Aedes aegypti) of N,N-diethyl-m-toluamide (DEET, 0.3 mg/cm², N =3) and a mixture of n-octanoic, n-nonanoic, and n-decanoic acids(C8C9C10, 0.2 mg/cm² each, N = 3) on skin. % % % % Test RepellencyRepellency Repellency Repellency Substance (0 hr) (2 hr) (4 hr) (8 hr)C8C9C10 93 ± 1 85 ± 4  70 ± 19 82 ± 26 DEET^(a) 95 ± 6 89 ± 10 83 ± 9  —

EXAMPLE 5: Mildness Additive for Formulations

[0082] Application of octanoic acid full strength to intact or abradedrabbit skin for 24 hours under occlusion produced moderate to severeirritation; full strength nonanoic acid produced moderate irritation;full strength decanoic acid produced moderate to severe irritation(Moreno, O. M., Reports to Research Institute for Fragrance Materials,Aug. 2, 1976, Aug. 22, 1977). When tested at 1% in petrolatum on theskin of human subjects, octanoic and decanoic acids produced noirritation or sensitization reactions. When tested at 12% in petrolatumon the skin of human subjects, nonanoic acid produced no irritation orsensitization reactions. Erythema was observed on the skin of humanmales after repeated applications of 0.5 M solutions of octanoic,nonanoic and decanoic acids in propanol solutions (7.2% w/v, 7.9% w/vand 8.6% w/v respectively) under occlusive conditions (Stillman, M. A.,Maibach, H. I. and Shalta, A. R., Relative irritancy of free fatty acidsof different chain length. Contact Dermatitis 1:65-69, 1975).

[0083] Solutions containing 5% octanoic acid, 5% nonanoic acid, and 5%decanoic acid (C8C9C10) in ethanol and volatile silicone fluid (DowCorning 345 fluid, CTFA designated cyclomethicone) were prepared. Anaqueous gel containing 5% of each acid was also prepared. Their skinirritancy was compared to that of a commercial insect repellent (creamformulation of 10% DEET, Skintastic, S. C. Johnson, Racine WHEREIN) onthe forearms of a male subject. C8C9C10 in alcohol and siliconesolutions were applied at a volume of 0.5 ml to gauze pads that wereplaced on separate 1 inch×1 inch areas of skin; the C8C9C10/gel andDEET/cream formulations were applied at a mass of 0.5 g to separatesites. All sites were covered with a semi-occlusive tape (Transpore, 3M,Minneapolis, Minn.). Four hours after applications, sites were uncoveredand washed with water. No erythema was observed with theC8C9C10/silicone formulation and slight erythema was observed with theDEET cream formulation; no erythema was observed at later time points(24, 48, 72 hours after application) for these two formulations. Incontrast, the C8C9C10/aqueous gel formulation caused a burning sensationafter application and this formulation, along with the C8C9C10/alcoholformulation resulted in erythema, sometimes severe, at 4, 24, 48 and 72hours.

[0084] A Primary Dermal Irritation study of C8C9C10/silicone formulationand the commercial DEET cream formulation was conducted on six rabbitsaccording to EPA, FIFRA Subdivision F guidelines. The protocol wassimilar to that outlined for the human exposure, except that applicationsites were totally occluded with a rubber dam for 4 hours. Bothformulations were rated as mildly irritating in this test.

[0085] Octanoic, nonanoic and decanoic acid clearly have the potentialto cause skin irritation and the degree of skin irritation will be afunction of the formulation. Alcohol and aqueous gel formulationscontaining 5% of each acid do not appear acceptable for use as an insectand arthropod repellent in humans; a the silicone formulation howeverwas found to be acceptable.

[0086] In addition to having the effect of reducing skin irritation,water insoluble silicon containing additives are known to impart waterrepellency to a topical formulation (Dow Corning Literature Code2223926, Dow Corning Corporation, Midland, Mich.).

[0087] Volatile silicon fluids are available commercially. For example,Dow Corning uses commercial designations of 244, 245, 246, 344 and 345,which are mixtures of polydimethylcyclosiloxanes (cyclomethicones) andare composed of tetramers (e.g. cyclotetrasiloxane,octamethylcyclotetrasiloxane), pentamers (e.g. cyclopentasiloxane,decamethylcyclopentasiloxane), and hexamers (e.g. cyclohexasiloxane,dodecamethylcyclohexasiloxane).

[0088] The volatility of the vehicle can be important as well as thevolatility of the active ingredients. The cyclomethicones are morevolatile than typical repellent molecules, and are slightly lessvolatile than water. The cyclomethicones have a long history of use incosmetic preparations. As vehicles, they allow good spreading of activeson the skin and will eventually evaporate. They are insoluble in water,so that resistance to water wash-off of actives is imparted. Thecyclomethicones can be turned into gels for ease of application to theskin. Gelling of a formulation of octanoic, nonanoic, and decanoic acids(5% each in 344 fluid) did not interfere with repellent activity againstmosquitoes in tests conducted as described in Example 3.

[0089] Dimethicone (hexamethyldisiloxane) has similar physicalproperties to the cyclomethicones and is also extensively used incosmetics. A variety of polydimethylsiloxanes, with higher molecularweight than the cyclomethicones or dimethicone, enjoy wide use incosmetics; however, because of their higher molecular weight, they areless volatile. They do provide alternative carriers to thecyclomethicones, or mixtures of the two can be used.

[0090] A wide variety of derivatives of the above compounds are obtainedby introduction of various functional groups, by copolymerization, or bycrosslinking and many of those can be used to make useful formulationsof the inventive insect and arthropod repellent.

[0091] Mixtures of the various silicone fluids, either with othersilicone fluids or non-silicon containing substances, are used in avariety of cosmetic preparations to impart special properties, toinclude water repellency and skin protection.

[0092] To insure that the addition of silicone fluid to the actives didnot interfere with mosquito repellency, a comparison of theC8C9C10/silicone formulation with a commercial insect repellentformulation was conducted. A commercial formulation of DEET (Skintastic,S. C. Johnson, Racine,) was applied to a 100 cm² area on the forearm of1 volunteer (subject 02) to give a dose of 0.3 mg/cm² of DEET. Aformulation of C8C9C10 (5% octanoic, 5% nonanoic, 5% decanoic in DowCorning 345 volatile silicone fluid) was applied to a 100 cm² on thesubject's other arm to give a dose of 0.3 mg/cm² total acids.Application sites were placed under the olfactometer at 1, 2 and 4 hoursafter treatment. Untreated areas on each arm were placed under theolfactometer at the completion of the treated area tests to check theavidity of the mosquitoes. Tests were done on four separate test days.The results are shown in FIG. 14. The inventive C8C9C10/siliconeformulation had repellency equal to the commercial formulation at the 1,2 and 4 hour points (ANOVA, Tukey Studentized Range Method, P=0.05).Interestingly, C8C9C10/silicon at 0.3 mg/cm² total actives producedrepellency (90±13% at 1 h, 81±14% at 2 h, and 74±22% at 4 hours) equalto unformulated C8C9C10 applied at 0.6 mg/cm² total actives (Table 8).

[0093] Thus, the invention provides a new formulation for use on humanskin to repel insects and arthropods. The formulation is based onchemicals normally found on the human skin and so has a natural feel. Itcombines carbon chains having insect repellent activity at differentvapor pressures, to achieve persistence over time on the skin andvolatility for effectiveness in the volume of air surrounding the skin.

EXAMPLE 6: Veterinary Uses

[0094] Animal productivity is known to be reduced as a result of bitinginsects and arthropods. For example, stable flies reduce milk productionby 5 to 10%. While the use of pesticides can sometimes provide a shortterm solution to this problem, the long term economic consequences ofdamage to non-target species, environmental pollution, and contaminationof the food chain can be severe. The C8C9C10/silicone formulationprovides a non-lethal and non-toxic method to protect animals as well ashumans from nuisance and disease-carrying insects. This formulation issuitable for use in standard hand-held sprayers and would imparts waterrepellency.

[0095] Specifically, formulation of C8C9C10 (5% octanoic, 5% nonanoic,5% decanoic acids) in Dow Corning 345 fluid was applied to membranesexposed to approximately 50 wild Stomoxys calcitrans (biting stable fly)contained in plastic tubes 8.5 cm tall and 5 cm in diameter. Themembranes were mounted over warm defribrinated sheep blood. Untreatedmembranes served as controls. Flies were observed for 15-20 minutes,anesthetized, placed on a chill table, and sorted according to whetherthey had engorged blood or not. No flies engorged blood when the freshlytreated membrane was tested and most flies became incapacitated;approximately 90% of flies exposed to the control membrane engorged(Table 9). A membrane treated with the repellent formulation 3 hoursprior to stable fly challenge also prevented all flies from engorging;approximately 50% of flies exposed to the control membrane engorged(Table 9). TABLE 9 Efficacy of formulation C8C9C10/DC345 (5% octanoic,5% nonanoic, 5% decanoic acids in Dow Corning 345 fluid) to preventengorgement of stable flies*. Pretreatment Percent Trial No. timeinterval Treatment Engorgement 1 0 h C8C9C10/DC345 0% 2 0 h None(control) 94%  3 3 h C8C9C10/DC345 0% 4 3 h None (control) 52% 

[0096] The inventive insect and arthropod repellent, formulated in avolatile silicone fluid, was shown to repel and incapcitate stableflies. This finding demonstrated that repellency was not limited tomosquitoes, but extends to other biting flies, insects, or arthropodsthus demonstrating the utility of the novel insect and arthropodrepellent for protecting pets and livestock as well as humans.

[0097] In summary, the present invention describes a novel insect andarthropod repellent that provides long lasting protection againstmosquitoes, and that is stable, commercially available, economicallycompetitive, safe (noted GRAS by the FDA).

[0098] The description of illustrative embodiments and best modes of thepresent invention is not intended to limit the scope of the invention.Various modifications, alternative constructions and equivalents may beemployed without departing from the true spirit and scope of theappended claims.

What is claimed is:
 1. An composition that repels insects or arthropodscomprising a combination of at least two organic molecular speciesnormally found on human skin.
 2. The composition of claim 1 comprisingmolecules having a polar group attached to a non-polar group, thenon-polar group comprising between about three and about twelve carbonatoms.
 3. The composition of claim 2 wherein the polar groups are chosenfrom the group consisting of carboxyls, alcohols, ketones, or lactones.4. The composition of claim 2 wherein the non-polar group comprisesunbranched chains.
 5. The composition of claim 2 wherein the non-polargroup comprises branched chains.
 6. The composition of claim 2 whereinthe at least two molecular species have at least two differentvolatilities.
 7. The composition of claim 6 wherein the mixture has askin surface evaporation rate that is at least equal to a minimumeffective evaporation rate.
 8. The composition of claim 7 wherein theevaporation rate of the mixture is at least equal to about 2 μg/cm²-hr.9. The composition of claim 7 wherein the evaporation rate of themixture is at least equal to about 10 μg/cm²-hr.
 10. The composition ofclaim 7 wherein the mixture maintains a skin surface evaporation ratethat is at least equal to a minimum effective evaporation rate for atleast two hours
 11. The composition of claim 7 wherein the mixturemaintains a skin surface evaporation rate that is at least equal to aminimum effective evaporation rate for at least five hours.
 12. Thecomposition of claim 7 wherein the mixture maintains a skin surfaceevaporation rate that is at least equal to a minimum effectiveevaporation rate for at least eight hours.
 13. The composition of claim7 wherein the molecules comprise a mixture of low volatility moleculeshaving a vapor pressure between about 0.1 mm mercury (Hg) and about 10mm Hg at 125° C. and high volatility molecules having between about 5 mmHg and about 100 mm Hg at 125° C.
 14. The composition of claim 13wherein the high volatility molecules comprise between about one percentand about ninety-nine percent of the active ingredients.
 15. Thecomposition of claim 13 wherein the high volatility molecules comprisebetween about ten percent and about ninety percent of the activeingredients.
 16. The composition of claim 13 wherein the high volatilitymolecules comprise between about forty percent and about sixty percentof the active ingredients.
 17. The composition of claim 13 wherein thelow volatility molecules comprise between about one percent and aboutninety-nine percent of the active ingredients.
 18. The composition ofclaim 13 wherein the low volatility molecules comprise between about tenpercent and about ninety percent of the active ingredients.
 19. Thecomposition of claim 13 wherein the low volatility molecules comprisebetween about forty percent and about sixty percent of the activeingredients.
 20. The composition of claim 13 wherein the molecules are amixture of octanoic acid and 4-methyloctanoic acid.
 21. The compositionof claim 20 further comprising isomers or homologs of octanoic acid and4-methyloctanoic acid.
 22. The composition of claim 13 wherein themolecules are a mixture of nonanoic acid and 4-methyloctanoic acid. 23.The compound of claim 22 further comprising isomers or homologs ofnonanoic acid and 4-methyloctanoic acid.
 24. The composition of claim 7wherein the molecules comprise a mixture of, a) low volatility moleculeshaving a vapor pressure between about 0.1 mm Hg and about 5 mm Hg at125° C.; b) intermediate volatility molecules having a vapor pressurebetween about 1 mm Hg and about 10 mm Hg at 125° C.; and (c) highvolatility molecules having a vapor pressure between about 8 mm Hg andabout 100 mm Hg at 125° C.; wherein the vapor pressure of the highvolatility molecule is always higher than the vapor pressure of theintermediate volatility molecule, which in turn is always higher thanthe vapor pressure of the low volatility molecule.
 25. The compositionof claim 24 wherein the molecules comprise a mixture of unbranched shortchain molecules having between about six and about eight carbon atomsper molecule, intermediate unbranched chain molecules having betweenabout nine carbon atoms per molecule, and long unbranched chainmolecules having between about nine and about twelve carbon atoms permolecule.
 26. The composition of claim 24 wherein the high volatilitymolecules comprise between about one percent and about ninety-ninepercent of the active ingredients.
 27. The composition of claim 24wherein the high volatility molecules comprise between about ten percentand about seventy percent of the active ingredients.
 28. The compositionof claim 24 wherein the high volatility molecules comprise between abouttwenty percent and about fifty percent of the active ingredients. 29.The composition of claim 24 wherein the intermediate volatilitymolecules comprise between about one percent and about ninety-ninepercent of the active ingredients.
 30. The composition of claim 24wherein the intermediate volatility molecules comprise between about tenpercent and about seventy percent of the active ingredients.
 31. Thecomposition of claim 24 wherein the intermediate volatility moleculescomprise between about twenty percent and about fifty percent of theactive ingredients.
 32. The composition of claim 24 wherein the lowvolatility molecules comprise between about one percent and aboutninety-nine percent of the active ingredients.
 33. The composition ofclaim 24 wherein the low volatility molecules comprise between about tenpercent and about seventy percent of the active ingredients.
 34. Thecomposition of claim 24 wherein the low volatility molecules comprisebetween about twenty percent and about fifty percent of the activeingredients.
 35. The composition of claim 24 wherein the mixturecomprises molecules having unbranched chains of eight carbons, moleculeshaving unbranched chains of nine carbons, and molecules havingunbranched chains of ten carbons per molecule.
 36. The composition ofclaim 35 wherein the molecules comprise saturated fatty acid chains. 37.The composition of claim 36 wherein there are about equal concentrationsof eight-carbon molecules, nine-carbon molecules, and ten-carbonmolecules.
 38. The composition of claim 6 further comprising a carriervehicle.
 39. The composition of claim 38 wherein the vehicle isnon-aqueous.
 40. The composition of claim 39 wherein the vehicle issilicone fluid.
 41. The composition of claim 38 wherein the percent ofactive ingredients is between about 1% and about 50%.
 42. Thecomposition of claim 38 wherein the percent of active ingredients isbetween about 5% and about 25%.
 43. The composition of claim 38 whereinthe percent of active ingredients is about 15%.
 44. The composition ofclaim 43 wherein the active ingredients comprise about five percentoctanoic acid, about five percent nonanoic acid, and about five percentdecanoic acid.
 45. An insect repellent comprising a combination oforganic molecules including a combination of two or more volatilecarboxylic acid molecules, wherein a) at least one of the molecules hasa vapor pressure between about 0.1 mm Hg and about 10 mm Hg at 125° C.;b) at least one other molecule has a vapor pressure between about 5 mmHg and about 100 mm Hg at 125° C.; and c) a dermatologically acceptablevehicle in which the carboxylic acid molecules are mixed, in aconcentration sufficient to repel insects.
 46. The insect repellant ofclaim 45 wherein the vehicle comprises a silicon-containing fluid. 47.An insect repellent comprising a combination of organic moleculesincluding a combination of at least three volatile carboxylic acidmolecules, wherein, a) one of the organic molecules has a vapor pressurebetween about 0.1 mm Hg and about 5 mm Hg at 125° C.; b) a second of theorganic molecules has a vapor pressure between about 1 mm Hg and about10 mm Hg at 125° C.; (c) a third of the organic molecules has a vaporpressure between about 8 mm Hg and about 100 mm Hg at 125° C.; and d) adermatologically acceptable vehicle in which the carboxylic acidmolecules are mixed, in a concentration sufficient to repel insects. 48.The insect repellent of claim 47 wherein the third of the organiccarboxylic acid molecules has a vapor pressure between about 8 mm Hg andabout 25 mm Hg at 125° C.
 49. The insect repellant of claim 47 whereinthe vehicle comprises a silicon-containing fluid.
 50. An insectrepellent comprising a combination of organic molecules including acombination of two or more volatile alcohol molecules, wherein a) atleast one of the molecules has a vapor pressure between about 0.1 mm Hgand about 10 mm Hg at 125° C.; b) at least one other molecule has avapor pressure between about 5 mm Hg and about 100 mm Hg at 125° C.; andc) a dermatologically acceptable vehicle in which the alcohol moleculesare mixed in, a concentration sufficient to repel insects.
 51. Theinsect repellent of claim 50 wherein the vehicle comprises asilicon-containing fluid.
 52. An insect repellent comprising acombination of organic molecules including a combination of at leastthree volatile alcohol molecules, wherein a) one of the organicmolecules has a vapor pressure between about 0.1 mm Hg and about 5 mm Hgat 125° C.; b) a second of the organic molecules has a vapor pressurebetween about 1 mm Hg and about 10 mm Hg at 125° C.; c) a third of theorganic molecules has a vapor pressure between about 8 mm Hg and about100 mm Hg at 125° C.; and d) a dermatologically acceptable vehicle inwhich the alcohol molecules are mixed in, a concentration sufficient torepel insects.
 53. The insect repellent of claim 52 wherein the third ofthe organic alcohol molecules has a vapor pressure between about 8 mm Hgand about 25 mm Hg at 125° C.
 54. The insect repellent of claim 52wherein the vehicle comprises a silicon-containing fluid.
 55. An insectrepellent comprising a combination of organic molecules including acombination of two or more volatile ketone molecules, wherein a) atleast one of the molecules has a vapor pressure between about 0.1 mm Hgand about 10 mm Hg at 125° C.; b) at least one other molecule has avapor pressure between about 5 mm Hg and about 100 mm Hg at 125° C.; andc) a dermatologically acceptable vehicle in which the ketone moleculesare mixed in, a concentration sufficient to repel insects.
 56. Theinsect repellent of claim 55 wherein the vehicle comprises asilicon-containing fluid.
 57. An insect repellent comprising acombination of organic molecules including a combination of at leastthree volatile ketone molecules, wherein a) one of the organic moleculeshas a vapor pressure between about 0.1 mm Hg and about 5 mm Hg at 125°C.; b) a second of the organic molecules has a vapor pressure betweenabout 1 mm Hg and about 10 mm Hg at 125° C.; c) a third of the organicmolecules has a vapor pressure between about 8 mm Hg and about 100 mm Hgat 125° C; and d) a dermatologically acceptable vehicle in which theketone molecules are mixed in, a concentration sufficient to repelinsects.
 58. The insect repellent of claim 57 wherein the third of theorganic ketone molecules has a vapor pressure between about 8 mm Hg andabout 25 mm Hg at 125° C.
 59. The insect repellent of claim 57 whereinthe vehicle comprises a silicon-containing fluid.
 60. An insectrepellent comprising a combination of organic molecules including acombination of two or more volatile lactone molecules, wherein a) atleast one of the molecules has a vapor pressure between about 0.1 mm Hgand about 10 mm Hg at 125° C.; b) at least one other molecule has avapor pressure between about 5 mm Hg and about 100 mm Hg at 125° C.; andc) a dermatologically acceptable vehicle in which the lactone moleculesare mixed in, a concentration sufficient to repel insects.
 61. Theinsect repellent of claim 60 wherein the vehicle comprises asilicon-containing fluid.
 62. An insect repellent comprising acombination of organic molecules including a combination of at leastthree volatile lactone molecules, wherein a) one of the organicmolecules has a vapor pressure between about 0.1 mm Hg and about 5 mm Hgat 125° C.; b) a second of the organic molecules has a vapor pressurebetween about 1 mm Hg and about 10 mm Hg at 125° C.; c) a third of theorganic molecules has a vapor pressure between about 8 mm Hg and about100 mm Hg at 125° C.; and d) a dermatologically acceptable vehicle inwhich the lactone molecules are mixed in, a concentration sufficient torepel insects.
 63. The insect repellent of claim 62 wherein the third ofthe organic lactone molecules has a vapor pressure between about 8 mm Hgand about 25 mm Hg at 125° C.
 64. The insect repellent of claim 62wherein the vehicle comprises a silicon-containing fluid.
 65. A methodfor repelling insects from the skin of animals comprising the steps of,a) combining at least two organic molecular species normally found onhuman skin, wherein the molecular species have a polar group attached toa non-polar group and the non-polar group comprises between about threeand about twelve carbon atoms and wherein the at least two molecularspecies have at least two different volatilities; b) adding adermatologically acceptable vehicle; and c) applying the mixture to ahuman's skin or an animal's fur or skin.